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Biomedical subjects

K Kanno

Publications and source records attributed to K Kanno.

At least 55 records · Page 3Linked to original sources
PubMed1994

Phenotypic change of endothelin receptor subtype in cultured rat vascular smooth muscle cells.

An endothelium-derived vasoactive peptide, endothelin (ET)-1, is a potent constrictor and mitogen for vascular smooth muscle cells (VSMC). To determine whether vascular ET receptor subtypes phenotypically change during in vitro culture conditions, we studied the expression of ET receptor subtypes, ET-induced phosphoinositide breakdown, and DNA synthesis in cultured rat VSMCs during serial passages. Binding studies using [125I]ET-1 as a radioligand revealed that the early passage (10th-15th) VSMCs possess predominantly ETA receptors, whereas the late passage (30th-35th) VSMCs possess predominantly ETB receptors in addition to ETA receptors. Northern blot analysis using cDNAs for rat ETA and ETB receptors as probes also demonstrated the predominant expression of ETA receptor mRNA in the early passage and ETB receptor mRNA in the late passage, whereas only ETA receptor mRNA was expressed in intact medium of rat aorta. ET-1 had a greater effect than ET-3 in stimulating inositol 1,4,5-trisphosphate formation, whereas ET-1 and ET-3 almost equipotently stimulated insitol 1,4,5-trisphosphate formation in the late passage VSMC even in the presence of an ETA receptor antagonist. ET-1-induced DNA synthesis was almost completely inhibited by an ETA receptor antagonist in the early passage VSMC. In contrast, ET-1, ET-3, and an ETB receptor agonist remarkably stimulated DNA synthesis in the late passage VSMC, which was completely inhibited by a nonselective ET receptor antagonist, but not by an ETA receptor antagonist. Our data provide the first evidence that a phenotypic change in VSMC in culture is concomitantly associated with a change in the ET receptor subtype that potentiates mitogenic activity and suggest that switching the ET receptor subtype from ETA to ETB during phenotypic change may in part contribute to the development of vascular lesions, such as in atherosclerosis.

Animals↗
PubMed1994

TA-2005, a novel, long-acting, and selective beta 2-adrenoceptor agonist: characterization of its in vivo bronchodilating action in guinea pigs and cats in comparison with other beta 2-agonists.

Relaxant effects of the beta 2-selective adrenoceptor agonist TA-2005 on bronchoconstriction in the anesthetized guinea pig and cat were evaluated in comparison with other known beta 2-adrenoceptor agonists. The ED50 values of intravenously administered TA-2005, procaterol, formoterol, isoproterenol, salbutamol, and salmeterol to inhibit the histamine-induced bronchoconstriction of the guinea pigs were 0.024, 0.053, 0.056, 0.099, 0.23, and 2.00 micrograms/kg, respectively, and those in serotonin-challenged cats were 0.019, 0.037, 0.039, 0.042, 0.13, and 0.52 micrograms/kg, respectively, in the same increasing order. When guinea pigs were passively sensitized with anti-ovalbumin antiserum, the ED50 values of TA-2005, formoterol, procaterol, and isoproterenol to inhibit the antigen-induced bronchoconstriction were 0.09, 0.30, 0.65, and 7.0 micrograms/kg, i.v., respectively, while those of TA-2005, procaterol, formoterol, and salbutamol in actively sensitized animals were 0.24, 0.25, 1.40, and 23.0 micrograms/kg. When TA-2005 was administered by inhalation to guinea pigs or by the intraduodenal route to cats, it exhibited a long-lasting inhibitory effect comparable or superior to the effects of salmeterol and formoterol. These data indicate that, among the known beta 2-adrenoceptor agonists examined, TA-2005 exerts the most potent bronchodilating effects with a long duration of action in vivo, and its potency ratios to the other reference drugs were greater in antigen- than spasmogen-induced bronchoconstriction models.

Administration, Inhalation↗
PubMed1994

Epididymis metastasis from colon carcinoma: a case report and a review of the Japanese literature.

A 56-year-old Japanese man in whom a descending colon carcinoma had been resected underwent a high orchitectomy for metastatic epididymis from the colon. Metastatic carcinoma from the digestive organs to the spermatic cord (SC) and/or the intrascrotal contents (ISC) is rare. Fifty-four Japanese patients with metastasis from the digestive organs to the SC and/or the ISC were analyzed. The most frequent primary site was the stomach and the most frequent metastatic site was the spermatic cord. Our patient was the first to exhibit metastasis from the colon to the epididymis. A primary site was identified in 24 patients subsequent to the metastatic tumor. Twenty patients had other organ metastasis. The prognosis for SC and/or ISC metastasis patients is poor. Our patients has survived for 18 months following his orchitectomy with no other organ metastasis (31 months after the primary operation). In our patient, monoclonal estrogen receptor staining was negative; however, further study must be undertaken.

Carcinoma↗
PubMed1994

[A case of hemifacial spasm associated with a cerebellar hematoma].

This is a report of a hemifacial spasm associated with a cerebellar hematoma. A 60 year-old female was admitted to our hospital due to severe vertigo and nausea. On admission, the neurological examination showed drowsy conscious level, cerebellar sign dominant on the left side, and left hemifacial spasm. CT scans disclosed a large hematoma in the left cerebellar hemisphere. An angiography revealed a dominant left PICA, but showed neither vascular malformation nor aneurysm. An emergency removal of the hematoma was carried out by using suboccipital craniectomy. Three days after the surgery, the patient's left hemifacial spasm disappeared completely. She had never suffered from left hemifacial spasm prior to this cerebellar bleeding. The hemifacial spasm was thought to be due to either the compression of the left facial nerve by the PICA which had been displaced by the cerebellar hematoma, or to the fact that the nucleus of the left facial nerve might have been stimulated by the hematoma, and the hemifacial spasm might have been caused as a result of the stimulation. The total removal of the hematoma and the postoperative CSF leakage might have decompressed the facial nerve. It was considered that this might be similar to microvascular decompression.

Cerebellar Diseases↗
PubMed1994

Effect of an AT1 receptor antagonist (CV-11974) on angiotensin II-induced cardiomyocyte hypertrophy in vitro.

Angiotensin (ANG) II, a potent vasoconstrictor is known to be a hypertrophic factor for cardiomyocytes. Recently, endothelin (ET)-1 has also been shown to be an autocrine/paracrine growth factor for cardiomyocytes. To determine the cellular mechanism by which ANG II induces cardiac hypertrophy, we studied the effects of ANG II on the gene expression of ET-1 and ET receptor subtypes (ETA, ETB), as well as its effects on the expression of immediate early oncogenes (c-fos, c-myc) in cultured rat cardiomyocytes in vitro. ANG II (10(-7) M) increased steady-state mRNA levels of ET-1 in the same manner as c-fos and c-myc during a short incubation period (0.5-1 h), while ANG II induced ETB receptor mRNA, but not ETA receptor mRNA, during a long incubation period (6-12 h). CV-11974, an antagonist of ANG II receptor type-1 (AT1), inhibited the ANG II-induced expression of c-fos, c-myc and ET-1 mRNAs, as well as that of ETB receptor mRNA, whereas PD-123319, an antagonist of the ANG II type-2 (AT2) receptor, failed to block such induction. CV-11974 similarly blocked ANG II-induced immediate-early oncogenes (c-fos, c-myc) in cultured rat vascular smooth muscle cells. Our findings indicate that ANG II immediately upregulates the cardiac ET-1 gene in the same manner as it does the immediate early protooncogenes, while the late induction of the ETB receptor, mainly via the cardiac AT1 receptor, suggests the involvement of endogenous ET-1 in ANG II-induced cardiac hypertrophy.

Angiotensin II↗
PubMed1993

Up-regulation of ETB receptor subtype mRNA by angiotensin II in rat cardiomyocytes.

The effect of angiotensin (ANG) II on the expression of endothelin (ET) receptor subtype (ETA, ETB) mRNA in cultured neonatal rat cardiomyocytes was studied. ANG II (10(-7) M) increased steady-state mRNA levels of ETB receptor, but not ETA receptor, during 6-12 hr incubation, whose effect was dose-dependent (10(-9)-10(-7) M). ANG II receptor type-1 (AT1) antagonist (CV-11974) completely inhibited the ANG II-induced up-regulation of ETB receptor, whereas the inhibitory effect by ANG II receptor type-2 (AT2) antagonist (PD 123319) was incomplete. These results suggest that ANG II up-regulates cardiac ETB receptor, predominantly via AT1 receptor.

Angiotensin II↗
PubMed1993

Chronological observation on the energy metabolism of skin flaps by 31P-MRS: a novel approach to evaluate the state of a flap.

Although much has been reported on the energy metabolism of various flaps, at present there is no practical noninvasive and nondestructive method to demonstrate chronologically the changes in phosphate compounds in the same subject during the healing process. A skin island flap was obtained from the dorsal side of the posterior extremities in each of 18 Wistar female rats, and a skin arterial island flap (vein included in the pedicle was ligated and divided) also was obtained from the same area in each of 15 Wistar female rats. Chronological changes of ATP, phosphocreatine, and inorganic phosphate were observed by 31P-MRS (magnetic resonance spectroscopy) using surface coils at various intervals ranging from 2 hours to 1 week after the operation. And pH was calculated based on the chemical shift values. The results showed that the PCr/Pi ratio recovered at 4 to 8 hours postoperatively in the survival group, whereas the PCr/Pi ratio lasted at the low level after the operations in the necrosis group. Magnetic resonance spectroscopy is used extensively in studies of brain, heart, and muscle, but we have found only a few papers dealing with magnetic resonance spectroscopy and none with in vivo study in the field of plastic and reconstructive surgery. Since nuclear magnetic resonance imaging is becoming a "bedside" test in the general hospitals, we consider that the PCr/Pi ratio obtained from 31P-MRS can be an effective, noninvasive, and simple method for clinical use in predicting and observing the viability of flaps at an early stage.

Adenosine Triphosphate↗
PubMed1993

Induction of nitric oxide synthase gene by interleukin in vascular smooth muscle cells.

To elucidate whether cytokines induce nitric oxide synthase in vascular smooth muscle cells, we studied the effects of human recombinant interleukin-1 beta on the synthesis and release of nitric oxide in cultured rat vascular smooth muscle cells by measurement of NO2-/NO3- levels. Furthermore, we performed Northern blot analysis using subcloned polymerase chain reaction products as probes for constitutive and inducible nitric oxide synthase. Interleukin-1 beta dose dependently (1 to 20 ng/mL) stimulated NO2-/NO3- production as a function of time. Northern blotting demonstrated the interleukin-1 beta-induced expression of messenger RNA for an inducible but not for the constitutive nitric oxide synthase after 3 hours. NG-Monomethyl L-arginine completely blocked the interleukin-1 beta-induced NO2-/NO3- production, the effect of which was reversed by L-arginine but not by D-arginine. Dexamethasone inhibited the interleukin-1 beta-induced NO2-/NO3- production in a dose-dependent manner (10(-9) to 10(-7) M) and the interleukin-1 beta-inducible nitric oxide synthase messenger RNA levels. Neither a calmodulin inhibitor (W-7) nor a protein kinase C inhibitor (staurosporine) showed any effects on the induction of nitric oxide synthase transcripts or production of NO2-/NO3- stimulated by interleukin-1 beta, whereas cycloheximide and actinomycin D completely inhibited the basal and stimulated NO2-/NO3- production. These data demonstrate for the first time that interleukin-1 beta induces gene expression of inducible nitric oxide synthase and its de novo protein synthesis in rat vascular smooth muscle cells, thereby leading to generation of nitric oxide via Ca2+/calmodulin-independent and protein kinase C-independent mechanisms.

Alkaloids↗
PubMed1993

Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells.

Endothelins (ET) produce endothelium-dependent vasodilation through nitric oxide (NO) synthesis. The present study was designed to elucidate the cellular mechanism by which ET induces synthesis and release of endothelium-derived NO by cultured bovine endothelial cells (EC). Binding studies revealed that bovine EC membrane had the binding sites of a novel agonist (BQ3020) for non-isopeptide-selective receptor subtype (ETB). Affinity labeling studies showed a major labeled band with the apparent molecular mass of 50 kD. Northern blot analysis demonstrated the expression of mRNA for ETB receptor. BQ3020 rapidly and dose dependently induced formation of inositol-1,4,5-triphosphate and increased intracellular Ca2+ concentrations in fura-2-loaded cells. Concomitantly, BQ3020 dose dependently stimulated production of both nitrate/nitrite (NOx) and cyclic GMP; a highly significant correlation existed between NOx and cGMP production. The stimulatory effect on NOx and cGMP production by ETB agonist was inhibited by NO synthase inhibitor monomethyl-L-arginine; this effect was reversed by coaddition of L-arginine, but not D-arginine. NOx and cGMP production stimulated by BQ3020 was inhibited by pretreatment with pertussis toxin. ETB agonist-induced NOx production was blocked by a calmodulin inhibitor and an intracellular Ca2+ chelator, but not by an extracellular Ca2+ chelator or a Ca2+ channel blocker. These data suggest that endothelins stimulate ETB receptor-mediated phosphoinositide breakdown via pertussis toxin-sensitive G-protein(s), which triggers release of intracellular Ca2+, thereby activating Ca2+/calmodulin-dependent NO synthase in EC.

Amino Acid Oxidoreductases↗
PubMed1993

Cellular mechanism of natriuretic peptides-induced inhibition of endothelin-1 biosynthesis in rat endothelial cells.

We studied the cellular mechanism by which natriuretic peptides inhibit the synthesis and release of endothelin-1 (ET-1) in cultured rat aortic endothelial cells (EC). Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) showed dose-dependent and equipotent effects on displacement of [125I]ANP binding and generation of cGMP production in rat EC, whereas C-type natriuretic peptide and biologically inactive ANP analog had lesser effects. ANP and BNP as well as 8-bromo-cGMP had potent inhibitory effects on immunoreactive ET-1 release, the transient increase in the intracellular Ca2+ concentration, and the formation of inositol 1,4,5-trisphosphate stimulated by thrombin in rat EC. A cGMP-dependent protein kinase inhibitor (KT5823), but not a cAMP-dependent protein kinase inhibitor (KT5720), completely abolished the inhibitory effect of ANP on thrombin-induced immunoreactive Et-1 release. Northern blot analysis using cDNA for rat prepro-ET-1 as a probe showed that ANP and 8-bromo-cGMP, but not C-type natriuretic peptide, inhibited thrombin-induced prepro-ET-1 mRNA expression, whose effect was abolished by KT5823. These data suggest that ANP and BNP inhibit the thrombin-induced synthesis and release of ET-1 in cultured rat aortic EC by blocking phosphoinositide breakdown, possibly via natriuretic peptides type A receptor-mediated cGMP-dependent mechanism.

Animals↗
PubMed1993

Differential sensitivity to interleukins of CD5+ and CD5- anti-DNA antibody-producing B cells in murine lupus.

We studied the effects of interleukins (IL) on in vitro IgM and IgG anti-DNA antibody production by splenic B cells from autoimmune disease-prone NZBxNZW (NZB/W) F1 mice. It was found that different interleukins regulate phenotypically distinct B cells producing separate isotype of anti-DNA antibodies. IL-2 slightly but significantly inhibited the production of IgM anti-DNA antibodies. IL-4 and IL-6 significantly enhanced the antibody production, but the effects were not so marked and inconsistent, particularly with respect to IL-6. By contrast, the effects of IL-5 were remarkable, particularly on splenic B cells from young mice. As for IgG anti-DNA antibodies, IL-6, but not other interleukins, markedly up-regulated the antibody production by splenic B cells from mice over 6 months of age, in a dose dependent fashion. Thus, the ability of B cells to produce IgG anti-DNA antibodies appears to be dependent on the surface expression of IL-6 receptor (IL-6R) at the ages when the mice begin to develop the disease. Studies of the surface phenotypes showed that while the IL-5-sensitive major IgM anti-DNA producers were CD5+Lp-3(CD43)-sIgM+, the IL-6-sensitive major IgG anti-DNA producers were CD5-Lp-3+sIgM-. However, significant amounts of IgG antibodies were also produced, in the presence of IL-6, by CD5+Lp-3+sIgM+, but not by CD5-Lp-3+sIgM+ B cells from 6-month-old mice. We suggest that surface phenotypes of anti-DNA antibody producers change from CD5+Lp-3-sIgM+IL-5R+, CD5+Lp-3+sIgM+IL-6R+ and subsequently to CD5-Lp-3+sIgM-(sIgG+)IL-6R+ in NZB/W F1 mice with aging.

Animals↗
PubMed1993

Estimation of the functional reserve of the human liver by urinary D-glucaric acid excretion after vitamin C administration.

The excretion of D-glucaric acid in the urine (uGA) correlates with the total liver content of hepatic cytochrome P-450, the metabolism of which depends on adenosine triphosphate (ATP) being produced by intrahepatic cellular mitochondria. Five cases of compensated liver cirrhosis group with less than 0.4 mg/kg/min of the maximum removal rate of indocyanine green (ICGR max), and 5 cases with normal hepatic function (control group), were monitored for uGA before and after P-450 activation induced by administration of 1 g of vitamin-C. Before vitamin-C administration, no differences in uGA excretion were observed comparing the cirrhosis with the control group. After administration of vitamin-C, the excretion of uGA was significantly lower in the cirrhosis group. The measurement of uGA is considered to represent vitamin-C induced activation by P-450, and is a new method for evaluation of the functional reserve of the liver.

Adenosine Triphosphate↗
PubMed1992

Cellular mechanism of thrombin on endothelin-1 biosynthesis and release in bovine endothelial cell.

We have studied the cellular mechanism responsible for induction of preproendothelin (preproET)-1 mRNA and release of ET-1 by thrombin in cultured bovine endothelial cells (ECs). Thrombin induced an immediate and dose-dependent formation of inositol-1,4,5-trisphosphate (IP3) with a concomitant increase in intracellular Ca2+ concentration ([Ca2+]i). The thrombin-induced ET-1 release was abolished either by a phospholipase C inhibitor, a protein kinase C (PKC) inhibitor, or an intracellular Ca(2+)-chelator, whereas a Ca(2+)-channel antagonist was ineffective. A selective thrombin inhibitor (argatroban) decreased IP3 formation and the increase in [Ca2+]i and ET-1 release stimulated by thrombin. Northern blot analysis revealed that thrombin-induced expression of preproET-1 mRNA was inhibited completely by a PKC inhibitor and partially by argatroban. These data suggest that thrombin is involved in the mechanism of preproET-1 mRNA expression and subsequent ET-1 release, possibly through activation PKC and mobilization of intracellular Ca2+ resulting from the receptor-mediated phosphoinositide breakdown in ECs.

Animals↗
PubMed1992

Sulfated alkyl oligosaccharides with potent inhibitory effects on human immunodeficiency virus infection.

Compounds with medium relative molecular masses active against human immunodeficiency virus (HIV) were synthesized. Sulfated alkyl oligosaccharides such as sulfated octadecyl maltohexaoside, sulfated dodecyl laminaripentaoside and sulfated dodecyl laminari-oligomer caused 50% inhibition of virus infection in the EC50 range of 0.4-0.7 microgram/mL in vitro using the MT-4 cell line and HIV-1HTLV-IIIB virus isolate, though sulfated oligosaccharides without alkyl groups showed low anti-HIV activities. This anti-HIV activity was close to the EC50 of 0.43 microgram/mL for a highly active sulfated polysaccharide curdlan sulfate which was reported to inhibit completely the HIV infection at a concentration as low as 3.3 micrograms/mL. These compounds were also active against HIV-2 and a clinically isolated HIV-1 with reduced AZT sensitivity. For such sulfated alkyl oligosaccharides, the mechanism of inhibition of HIV infection was assumed to be the inhibition of HIV binding to the cell and to some extent the interaction of the alkyl portion with the lipid bilayer of the virus.

Amino Acid Sequence↗
PubMed1992

Endothelin receptors in human parathyroid gland.

We studied whether specific receptors for endothelins (ETs) exist in human parathyroid tissues and whether ETs may have any effect on secretion of PTH from parathyroid cells. Binding studies using [125I]ET-1 to the parathyroid membranes obtained from patients with hyperparathyroidism (2 adenomas, 2 hyperplasias) revealed that ET-1 competitively inhibited the binding of [125I]ET-1 to the membranes (the apparent Kd: 62 +/- 18 pM), whereas ET-3 showed biphasic and less steep inhibition curve than ET-1 in all tissue membranes examined. Northern blot analysis of poly(A)+ RNA from the parathyroid adenoma clearly demonstrated gene expression of both ETA and ETB receptors as well as preproET-1. ET-1 inhibited basal PTH secretion from dispersed adenoma cells more potently than ET-3. The present study clearly demonstrates the presence of both ETA and ETB receptor subtypes in human parathyroid tissues through which ETs may modulate PTH secretion in an autocrine and/or paracrine manner.

Adenoma↗
PubMed1992

Concomitant expression of receptor subtype and isopeptide of endothelin by human adrenal gland.

We studied whether specific receptors for endothelin (ET) isopeptide exist in human aldosterone-producing adenoma and normal adrenal cortex, and whether ET isopeptides are produced by human adrenal gland. Competitive binding studies using [125I]ET-1 as a radioligand revealed the presence of a single class of high-affinity binding sites for ET-1 with the apparent KD of 70 +/- 31 pM and Bmax of 226 +/- 139 fmol/mg protein in adenoma membranes almost comparable to those in adjacent normal cortex. The apparent Ki for ET-2 and ET-3 were 89 +/- 33 pM and 82 +/- 16 pM, respectively. Northern blot analysis of poly(A)+ RNA of adenoma and adjacent normal cortex using cDNAs for ET receptor subtype (ETA, ETB) and ET isopeptide (ET-1, ET-3) as probes revealed that ETA and ETB receptors as well as ET isopeptides (preproET-1, preproET-3) are concomitantly expressed in both tissues. Our data demonstrate for the first time that ET receptor subtype (ETA and ETB) and ET isopeptide (ET-1 and ET-3) are concomitantly expressed by human adrenal cortex, suggesting the potential role of ETs as a local mediator in human adrenal gland.

Adenoma↗
PubMed1992

Effects of three distinct natriuretic peptides on receptor binding and guanylate cyclase activities in rat glioma cells.

Receptor binding and cyclic GMP generation by three distinct natriuretic peptides (ANP, BNP, CNP) were studied in a cultured rat glioma cell line (C6). Binding studies revealed the presence of high-affinity binding sites for three natriuretic peptides with almost comparable affinities. In contrast, CNP and BNP were almost equipotent in stimulating intracellular cyclic GMP generation over the low concentration range, but CNP caused further elevation in the high concentration range, whereas ANP was minimally effective. Our data suggest that the glioma cells possess receptors more responsive to CNP than ANP and BNP despite no apparent correlation between receptor binding affinities and cyclic GMP responses.

Animals↗